Fungal polyketides are a family of secondary metabolites synthesized by molds from acetate via the acetate-polymalonate pathway. Among them, aflatoxins and sterigmatocystin have been identified as widespread mycotoxins responsible for high incidence of human diseases including cancer, large numbers of animal deaths, and significant loss in agricultural productivity. In this proposed research, the biosynthetic mechanisms of aflatoxins will be used as a model to elucidate biochemical events involved in the synthesis of fungal polyketides, the metabolic fate of aflatoxins and sterigmatocystin in the rhesus monkey will be determined under conditions which simulate actual human exposures to establish their mode of action and to estimate human response to these toxins, and the chicken embryos and the auxotrophic mutants of bacteria will be used to determine the acute toxicity, teratogenicity, mutagenicity, and carcinogenicity of the biosynthetic intermediates and the monkey metabolites of aflatoxins and sterigmatocystin. Thus, for those fungal polyketides deemed significant, research priorities can be established and areas of further investigation can be defined. The possiblity of inhibiting a common step in the biosynthetic pathway for polyketides by a single agent to suppress formation of a spectrum of mycotoxins will be examined. The overall objective is to expedite discovery and control of toxic fungal polyketides as foodborne mycotoxins.